In this project, we propose that subchronic exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), induces oxidative stress with the production of oxidative tissue damage and changes in the antioxidant defense mechanisms and the aminergic systems in various regions of the brain. We also propose that antioxidants, such as vitamin E succinate and ellagic acid provide protection against these effects. To test this hypothesis, groups of female Sprague Dawley rats will be treated p.o., with daily doses of TCDD for 13 weeks and will then be sacrificed at the end of this period. Various regions of the brain will be dissected and assayed for the determination of the biomarkers of oxidative stress, as well as the levels of different monoamines and their metabolites. The formation of reactive oxygen species in brain tissues will be determined using the cytochrome c reduction assay, and the induction of the processes of lipid peroxidation and DNA-single strand breaks (SSB) will be measured using the thiobarbituric acid reactive substances (TBARS) assay and the alkaline elution technique, respectively. The levels of glutathione and the activities of various antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and catalase will be also determined, using established biochemical assays. The levels of different biogenic amines in the brain regions will be determined using high performance liquid chromatography (HPLC). The protective effects of selected antioxidants, namely vitamin E succinate and ellagic acid against TCDD-induced oxidative stress in the brains of mice, will also be assessed. The results of the study will help future investigations of the body functions that are associated with the affected brain regions, which will provide tools for early detection of TCDD-intoxication. Furthermore, the study will be the first to investigate the protection by antioxidants against TCDD-induced effects on the brain, which may lead to new preventive measures against TODD-induced brain damage in exposed human populations.